Mutagenetix > Incidental Mutation

Incidental Mutation 'R0835:Slc12a5'

77791

Institutional Source

Beutler Lab

Gene Symbol

Slc12a5

Ensembl Gene

ENSMUSG00000017740

Gene Name

solute carrier family 12, member 5

Synonyms

KCC2

MMRRC Submission

039014-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0835 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

164802766-164841651 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 164835958 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 892 (I892N)

Ref Sequence

ENSEMBL: ENSMUSP00000144623 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000099092] [ENSMUST00000202136] [ENSMUST00000202223] [ENSMUST00000202479] [ENSMUST00000202623]

AlphaFold

Q91V14

Predicted Effect

possibly damaging
Transcript: ENSMUST00000099092
AA Change: I869N

PolyPhen 2 Score 0.858 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000096690
Gene: ENSMUSG00000017740
AA Change: I869N

Domain	Start	End	E-Value	Type
low complexity region	10	22	N/A	INTRINSIC
low complexity region	77	90	N/A	INTRINSIC
Pfam:AA_permease	102	304	5.2e-22	PFAM
Pfam:AA_permease_2	364	632	1e-17	PFAM
Pfam:AA_permease	389	676	1.9e-42	PFAM
Pfam:SLC12	688	814	2.1e-19	PFAM
Pfam:SLC12	807	959	1.8e-20	PFAM
low complexity region	978	1002	N/A	INTRINSIC
Pfam:SLC12	1009	1115	2.1e-15	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000137302

Predicted Effect

probably benign
Transcript: ENSMUST00000202136

SMART Domains

Protein: ENSMUSP00000143973
Gene: ENSMUSG00000017740

Domain	Start	End	E-Value	Type
low complexity region	10	22	N/A	INTRINSIC
low complexity region	77	90	N/A	INTRINSIC
Pfam:AA_permease	102	175	2.5e-10	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000202223
AA Change: I892N

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000143870
Gene: ENSMUSG00000017740
AA Change: I892N

Domain	Start	End	E-Value	Type
low complexity region	11	19	N/A	INTRINSIC
low complexity region	100	113	N/A	INTRINSIC
Pfam:AA_permease	125	327	1e-19	PFAM
Pfam:AA_permease_2	386	655	4.5e-15	PFAM
Pfam:AA_permease	412	699	3.7e-40	PFAM
Pfam:SLC12	711	837	7.2e-17	PFAM
Pfam:SLC12	830	982	6.2e-18	PFAM
low complexity region	1001	1025	N/A	INTRINSIC
Pfam:SLC12	1030	1133	8.6e-13	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000202479

SMART Domains

Protein: ENSMUSP00000144540
Gene: ENSMUSG00000017740

Domain	Start	End	E-Value	Type
low complexity region	10	22	N/A	INTRINSIC
low complexity region	77	90	N/A	INTRINSIC
Pfam:AA_permease	102	176	5.2e-10	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000202623
AA Change: I892N

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000144623
Gene: ENSMUSG00000017740
AA Change: I892N

Domain	Start	End	E-Value	Type
low complexity region	11	19	N/A	INTRINSIC
low complexity region	100	113	N/A	INTRINSIC
Pfam:AA_permease	125	327	5.3e-22	PFAM
Pfam:AA_permease_2	386	655	1.2e-17	PFAM
Pfam:AA_permease	412	699	2e-42	PFAM
Pfam:SLC12	711	837	2.1e-19	PFAM
Pfam:SLC12	830	982	1.8e-20	PFAM
low complexity region	1001	1025	N/A	INTRINSIC
Pfam:SLC12	1032	1138	2.2e-15	PFAM

Coding Region Coverage

1x: 99.2%
3x: 98.4%
10x: 96.2%
20x: 90.7%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] K-Cl cotransporters are proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The protein encoded by this gene is an integral membrane K-Cl cotransporter that can function in either a net efflux or influx pathway, depending on the chemical concentration gradients of potassium and chloride. The encoded protein can act as a homomultimer, or as a heteromultimer with other K-Cl cotransporters, to maintain chloride homeostasis in neurons. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Sep 2008]
PHENOTYPE: Mice homozygous for disruptions in this gene die within a few minutes of birth of respiratory failure resulting from a motor nerve defect. Mice homozygous for a hypomorphic allele display postnatal lethality and tonic-clonic seizures. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 75 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700034J05Rik	G	T	6: 146,855,036 (GRCm39)		probably benign	Het
Abca16	A	G	7: 120,065,007 (GRCm39)	T555A	probably benign	Het
Abca4	A	T	3: 121,919,862 (GRCm39)	D1048V	probably damaging	Het
Abcf2	G	T	5: 24,779,251 (GRCm39)	T99N	probably damaging	Het
Acan	A	T	7: 78,763,980 (GRCm39)	S2119C	probably damaging	Het
Adgre4	G	A	17: 56,106,637 (GRCm39)	C292Y	probably damaging	Het
Alk	A	G	17: 72,176,837 (GRCm39)	F1489S	probably damaging	Het
Ampd2	A	G	3: 107,983,818 (GRCm39)	V573A	possibly damaging	Het
Aoc1	T	C	6: 48,882,448 (GRCm39)	F130S	probably damaging	Het
Bbs2	A	T	8: 94,801,887 (GRCm39)	I554N	probably damaging	Het
Cacna2d4	C	T	6: 119,284,247 (GRCm39)	R745W	probably damaging	Het
Cbfa2t3	T	C	8: 123,374,517 (GRCm39)	H76R	probably benign	Het
Cdc14a	G	T	3: 116,122,171 (GRCm39)	N216K	probably benign	Het
Cep126	T	C	9: 8,130,224 (GRCm39)	Y69C	probably damaging	Het
Cep135	A	T	5: 76,763,553 (GRCm39)	R514S	probably benign	Het
Cfi	A	T	3: 129,662,191 (GRCm39)	Y390F	probably damaging	Het
Chd8	T	C	14: 52,441,482 (GRCm39)	D870G	probably benign	Het
Clptm1	A	G	7: 19,369,599 (GRCm39)	V437A	possibly damaging	Het
Coro2b	T	C	9: 62,333,119 (GRCm39)	N422S	possibly damaging	Het
Coro7	T	C	16: 4,450,118 (GRCm39)	E577G	probably benign	Het
Crh	G	A	3: 19,748,528 (GRCm39)	P38L	probably benign	Het
Ctif	T	A	18: 75,568,407 (GRCm39)	D577V	probably damaging	Het
Deup1	T	A	9: 15,511,047 (GRCm39)	Q244L	probably damaging	Het
Dhx16	A	G	17: 36,192,581 (GRCm39)	E171G	probably damaging	Het
Dnah11	A	C	12: 117,880,523 (GRCm39)	Y3866D	probably damaging	Het
Dync1i2	C	T	2: 71,081,316 (GRCm39)	L508F	probably damaging	Het
Dync2h1	T	A	9: 7,116,642 (GRCm39)		probably null	Het
E2f4	C	T	8: 106,027,140 (GRCm39)	Q235*	probably null	Het
Eif2b3	A	G	4: 116,916,002 (GRCm39)	H203R	probably damaging	Het
Epha5	A	T	5: 84,534,101 (GRCm39)	W77R	probably damaging	Het
Gpx6	C	T	13: 21,501,238 (GRCm39)	P109S	probably damaging	Het
Gsdmc4	A	T	15: 63,765,649 (GRCm39)	V300E	probably damaging	Het
Gspt1	A	C	16: 11,056,802 (GRCm39)	S198A	probably benign	Het
Ift70a2	T	C	2: 75,808,494 (GRCm39)	N6S	probably benign	Het
Itpk1	C	T	12: 102,641,707 (GRCm39)	V39M	probably damaging	Het
Kremen2	G	T	17: 23,961,811 (GRCm39)	P232Q	probably damaging	Het
Lamtor4	C	A	5: 138,257,320 (GRCm39)	T74K	probably benign	Het
Mbtd1	T	A	11: 93,822,665 (GRCm39)	F492I	probably benign	Het
Mroh1	G	T	15: 76,336,083 (GRCm39)	V1486F	probably damaging	Het
Myg1	G	A	15: 102,240,537 (GRCm39)	V76M	probably damaging	Het
Myo16	G	T	8: 10,322,766 (GRCm39)	Q65H	probably damaging	Het
Ncapg	A	G	5: 45,838,790 (GRCm39)	E487G	probably damaging	Het
Ncoa5	T	C	2: 164,844,714 (GRCm39)	E332G	probably damaging	Het
Nek6	T	A	2: 38,459,643 (GRCm39)	I162N	possibly damaging	Het
Nwd2	C	A	5: 63,957,473 (GRCm39)	R268S	probably damaging	Het
Or4c11	T	C	2: 88,695,345 (GRCm39)	V132A	probably benign	Het
Or9a7	T	C	6: 40,521,272 (GRCm39)	I214V	probably benign	Het
Palm3	T	G	8: 84,754,776 (GRCm39)	S141A	probably benign	Het
Pbrm1	T	C	14: 30,789,536 (GRCm39)	F728L	probably damaging	Het
Phf3	A	G	1: 30,869,632 (GRCm39)	V472A	probably benign	Het
Plekha5	T	A	6: 140,514,576 (GRCm39)	L35*	probably null	Het
Ppp1r16a	C	T	15: 76,577,869 (GRCm39)	Q328*	probably null	Het
Ppp6r2	G	A	15: 89,152,785 (GRCm39)	E309K	possibly damaging	Het
Ptpn6	T	A	6: 124,704,499 (GRCm39)		probably null	Het
Rasgrf1	T	C	9: 89,882,824 (GRCm39)	V882A	probably benign	Het
Ryr3	T	G	2: 112,480,483 (GRCm39)	E4335D	probably benign	Het
Slc22a2	G	A	17: 12,831,318 (GRCm39)	M369I	probably benign	Het
Sox10	A	T	15: 79,040,641 (GRCm39)	Y300N	probably damaging	Het
Speg	T	C	1: 75,352,318 (GRCm39)	F79L	probably benign	Het
Sult1b1	T	A	5: 87,665,311 (GRCm39)	I208L	probably benign	Het
Syt9	A	G	7: 107,105,737 (GRCm39)	N460S	probably benign	Het
Tecpr1	T	A	5: 144,149,410 (GRCm39)	N339I	possibly damaging	Het
Tmem63b	C	A	17: 45,971,870 (GRCm39)	D782Y	possibly damaging	Het
Ttn	T	C	2: 76,725,105 (GRCm39)		probably benign	Het
Upk3bl	G	T	5: 136,086,185 (GRCm39)	R40S	probably benign	Het
Usp28	T	C	9: 48,912,824 (GRCm39)	I25T	probably damaging	Het
Vmn2r27	A	G	6: 124,177,583 (GRCm39)	Y474H	probably damaging	Het
Vps13a	A	T	19: 16,712,246 (GRCm39)		probably null	Het
Wdr36	A	T	18: 32,982,135 (GRCm39)	N371I	possibly damaging	Het
Wnt7b	A	G	15: 85,421,978 (GRCm39)	F228S	probably damaging	Het
Xirp2	T	C	2: 67,338,254 (GRCm39)	I165T	possibly damaging	Het
Zan	T	G	5: 137,406,659 (GRCm39)		probably benign	Het
Zfp760	A	G	17: 21,942,559 (GRCm39)	D578G	possibly damaging	Het
Zfyve19	T	A	2: 119,041,266 (GRCm39)	S61T	probably benign	Het
Zfyve9	T	C	4: 108,575,866 (GRCm39)	D405G	probably damaging	Het

Other mutations in Slc12a5

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00324:Slc12a5	APN	2	164,839,041 (GRCm39)	missense	probably damaging	1.00
IGL00425:Slc12a5	APN	2	164,825,201 (GRCm39)	missense	probably damaging	1.00
IGL00976:Slc12a5	APN	2	164,821,224 (GRCm39)	missense	probably damaging	1.00
IGL01654:Slc12a5	APN	2	164,815,675 (GRCm39)	missense	possibly damaging	0.91
IGL01905:Slc12a5	APN	2	164,832,301 (GRCm39)	missense	probably benign	0.02
IGL02205:Slc12a5	APN	2	164,838,399 (GRCm39)	missense	probably benign	0.03
IGL02510:Slc12a5	APN	2	164,824,728 (GRCm39)	splice site	probably benign
IGL02746:Slc12a5	APN	2	164,816,836 (GRCm39)	missense	probably benign	0.01
G1Funyon:Slc12a5	UTSW	2	164,835,611 (GRCm39)	missense	probably damaging	0.98
R0051:Slc12a5	UTSW	2	164,828,583 (GRCm39)	missense	probably damaging	1.00
R0254:Slc12a5	UTSW	2	164,839,165 (GRCm39)	critical splice donor site	probably null
R0412:Slc12a5	UTSW	2	164,835,982 (GRCm39)	missense	probably benign	0.05
R0587:Slc12a5	UTSW	2	164,818,453 (GRCm39)	missense	probably damaging	1.00
R0932:Slc12a5	UTSW	2	164,838,805 (GRCm39)	splice site	probably benign
R1643:Slc12a5	UTSW	2	164,835,947 (GRCm39)	missense	probably benign	0.01
R1700:Slc12a5	UTSW	2	164,834,296 (GRCm39)	missense	possibly damaging	0.94
R1760:Slc12a5	UTSW	2	164,838,048 (GRCm39)	missense	probably damaging	0.99
R2063:Slc12a5	UTSW	2	164,839,067 (GRCm39)	missense	probably damaging	1.00
R2293:Slc12a5	UTSW	2	164,834,250 (GRCm39)	missense	probably benign	0.03
R2412:Slc12a5	UTSW	2	164,818,382 (GRCm39)	critical splice donor site	probably null
R3035:Slc12a5	UTSW	2	164,822,178 (GRCm39)	missense	probably benign	0.06
R3116:Slc12a5	UTSW	2	164,838,101 (GRCm39)	splice site	probably null
R3412:Slc12a5	UTSW	2	164,810,351 (GRCm39)	missense	probably benign	0.26
R3788:Slc12a5	UTSW	2	164,835,695 (GRCm39)	missense	probably damaging	1.00
R4039:Slc12a5	UTSW	2	164,834,250 (GRCm39)	missense	probably benign	0.03
R4174:Slc12a5	UTSW	2	164,821,410 (GRCm39)	missense	probably damaging	1.00
R4492:Slc12a5	UTSW	2	164,821,263 (GRCm39)	missense	probably benign	0.08
R4608:Slc12a5	UTSW	2	164,815,685 (GRCm39)	missense	probably damaging	0.99
R4750:Slc12a5	UTSW	2	164,824,851 (GRCm39)	missense	probably benign	0.06
R4994:Slc12a5	UTSW	2	164,825,285 (GRCm39)	splice site	probably null
R5103:Slc12a5	UTSW	2	164,834,353 (GRCm39)	missense	probably damaging	1.00
R5539:Slc12a5	UTSW	2	164,829,126 (GRCm39)	missense	possibly damaging	0.94
R5632:Slc12a5	UTSW	2	164,829,141 (GRCm39)	missense	possibly damaging	0.86
R5771:Slc12a5	UTSW	2	164,815,688 (GRCm39)	missense	possibly damaging	0.88
R6139:Slc12a5	UTSW	2	164,834,231 (GRCm39)	missense	probably damaging	0.98
R6336:Slc12a5	UTSW	2	164,834,384 (GRCm39)	splice site	probably null
R6581:Slc12a5	UTSW	2	164,829,035 (GRCm39)	missense	probably damaging	1.00
R6706:Slc12a5	UTSW	2	164,830,509 (GRCm39)	missense	probably damaging	1.00
R6886:Slc12a5	UTSW	2	164,824,825 (GRCm39)	missense	probably benign
R7134:Slc12a5	UTSW	2	164,816,878 (GRCm39)	missense	probably damaging	1.00
R7310:Slc12a5	UTSW	2	164,834,360 (GRCm39)	missense	probably damaging	1.00
R7402:Slc12a5	UTSW	2	164,824,852 (GRCm39)	missense	probably benign	0.01
R8079:Slc12a5	UTSW	2	164,834,372 (GRCm39)	missense	probably damaging	1.00
R8301:Slc12a5	UTSW	2	164,835,611 (GRCm39)	missense	probably damaging	0.98
R9105:Slc12a5	UTSW	2	164,838,114 (GRCm39)	missense	probably benign
R9132:Slc12a5	UTSW	2	164,835,876 (GRCm39)	intron	probably benign
R9431:Slc12a5	UTSW	2	164,832,178 (GRCm39)	missense	possibly damaging	0.95
R9580:Slc12a5	UTSW	2	164,816,896 (GRCm39)	missense	probably damaging	0.99
R9677:Slc12a5	UTSW	2	164,834,246 (GRCm39)	missense	possibly damaging	0.66

Predicted Primers

PCR Primer
(F):5'- CCTGCTGGTCACCAAGAATGTTTCC -3'
(R):5'- GAAGGCGACCTGTATCATCCACTG -3'

Sequencing Primer
(F):5'- CAATGTCCATGTAGGTGTGTCC -3'
(R):5'- GTATCATCCACTGACGGCTATG -3'

Posted On

2013-10-16